Clinical trials

Alcohol addiction (AD) is a chronic relapsing disorder with currently limited pharmacological treatment options. Alcohol craving, a hallmark symptom of AD that drives relapse in patients, is only insufficiently treated by existing medication. One promising new compound for the treatment of alcohol craving in AD is Cannabidiol (CBD), which showed beneficial effects on alcohol craving in preliminary clinical studies. Additionally, CBD seems to be a particularly promising candidate for enhancing the effects of established medication, specifically Naltrexone (NTX), an opioid-antagonist, which is approved for AD treatment, due to the synergistic effects of the combination of Cannabidiol plus Naltrexone on alcohol consumption that were shown by preclinical studies. The proposed three-armed, 1:1:1 randomized, double-blind, placebo-controlled parallel group, multicentric phase II trial seeks to test the putative synergistic effects of combined CBD (800mg) + oral NTX (50mg) against CBD (1200mg) + oral NTX (50mg) against Placebo + oral NTX (50mg) on alcohol craving (primary outcome) in male and female patients with AD that suffer from high alcohol craving. The trial seeks to test the effects of the innovative combination of CBD plus NTX against Placebo plus NTX on alcohol craving over a 14-day treatment period, which is embedded in a standardized addiction treatment program according to current treatment guidelines, in order to estimate the added value of treatment with CBD on alcohol craving. Quality of life and neurobiological and biochemical markers for craving will serve as secondary outcomes, because they show strong associations to treatment outcome and relapse risk. Collection and analysis of follow-up data (28 days, 42 days, 105 days, 196 days) will be performed to determine whether treatment effects relate to patient outcome.

Individuals with Borderline Personality Disorder (BPD) experience intensive, instable negative emotions. Hyperactivity of the amygdala is assumed to drive exaggerated emotional responses in BPD. Neurofeedback is an endogenous neuromodulation method to address the imbalance of neural circuits. Downregulation of amygdala hyperactivation with neurofeedback may ameliorate dysregulated emotions in BPD. The BrainSTEADy trial is designed to determine whether amygdala-fMRI-BOLD neurofeedback has a specific effect on affect instability in BPD beyond nonspecific benefit.

Schizophrenia is one of the most severe and costliest mental disorders in terms of human suffering and societal expenditure. About 15-30% of patients do not respond to all known antipsychotics, including clozapine, the current gold-standard in these cases. Hence, a recent Cochrane review stated that the quality of the existing studies is too poor to recommend any intervention in addition to clozapine and that new, randomized controlled trials independent from the pharmaceutical industry need to be performed to substantially improve patient care. Although electroconvulsive therapy (ECT) was initially used to treat schizophrenia, it is nowadays by far underused in the therapy of schizophrenia in many countries. ECT is well known to be highly effective in clozapine-treatment-resistant schizophrenia (CRS), and synergistic effects of clozapine and ECT have been demonstrated. However, relapse rates after successful courses of ECT are still very high, and evidence for maintenance ECT (mECT) in CRS is scarce at best. In a multi-center trial the investigators aim to examine the effectiveness of mECT in treatment-resistant patients with schizophrenia who improved after a course of routine ECT. If mECT will lead to a later timepoint of relapse and/or to a higher proportion of relapse-free patients compared to those undergoing treatment as usual, this trial would have an enormous impact on therapeutic strategies for "treatment-resistant" patients and would induce a profound change of current treatment guidelines, where ECT still ranks at the level of ultima ratio, despite accumulating evidence suggesting otherwise.

The aim of this project is to investigate the potential of transcranial direct current stimulation (tDCS) to reduce cognitive deficits and substance craving in individuals with substance use disorders (SUD), with a focus on alcohol use disorder (AUD). Patients of any gender between the ages of 18 and 65 are examined who are in our inpatient and day clinic settings for a standard detoxification treatment program. As there are conflicting findings regarding the effective settings for tDCS as an adjunctive treatment in SUD (e.g., effects on inhibitory control seem to be sensitive to current direction), the aim is to examine and compare three different active tDCS conditions, a sham tDCS condition (placebo), inhibition training, and a control group of patients receiving only standard detoxification treatment. The aim is to identify the optimal electrode placement and current direction to positively influence both inhibitory control and craving, leading to improved treatment outcomes such as longer abstinence periods or reduced substance use after relapse.

The goal of this observational study is to investigate longitudinal stress response profiles and adaptive versus non-adaptive stress responses in alcohol use disorder. The main questions the projects aims to answer are: What are the neurobehavioral underpinnings of adaptive stress responses and resilience to repeated stress exposure with regards to: * alcohol craving? * alcohol use? * their modulation by prior stress exposure, social interactions, coping strategies and individual health behavior? Participants will: * be exposed to an established experimental stress-induction protocol, the Trier Social Stress Test * be exposed to their favorite drink in a bar lab environment * be assessed using fMRI to determine their neural alcohol cue reactivity, response inhibition, and emotion processing * conduct an ambulatory phase to assess stressors, alcohol craving, substance use and details on social interactions, health behavior and coping strategies using ecological momentary assessment tools.

Electroconvulsive therapy (ECT) induces a cerebral seizure by electrical stimulation under general anesthesia and muscle relaxation, is regarded as a highly efficient (for specific and severe psychiatric disorders) and extremely safe modern treatment option. Alzheimer´s disease (AD) is a neurodegenerative disorder which is characterized by progressive cognitive deterioration accompanied by declining activities of daily living, by a variety of behavioral disturbances and by neuropsychiatric symptoms. The clinical progression of disease can be delayed by pharmaceutical therapies like acetylcholinesterase inhibition (e.g. rivastigmine) for 6 to 12 months at most. Along with the well-known biomarkers of AD (Aß- and tau-proteins) a lower brain-derived neurotrophic factor (BDNF) level is since recently being considered as a negative predictor for the further disease course. In animal experimental studies it was possible to arrest the disease progression with the aid of neurotrophic substances. Many single studies, but also a number of meta-analyses show primary gray matter atrophy in hippocampal, parahippocampal and medial temporal brain regions. Strikingly, ECT yields exact opposite effects to those caused by AD: an ECT series leads to an increase of serum BDNF-levels in patients. Parallel to this observation evidence exists for gray matter volume gain after an ECT series, especially for the hippocampus. There is sufficient clinical experience regarding the use of ECT in AD-patients, mainly on the basis of following indications: a) affective disorders and b) behavioral disturbances. A positive effect of ECT on the symptoms of agitation and aggression was assessed in AD patients alongside with a very good tolerability. To investigate the potential salutary effects of ECT on AD the investigators designed a pilot study with the following concept: Patients with a confirmed AD diagnosis and preexisting stable antidementia medication over at least 6 months will receive a modified maintenance ECT over a total of 27 weeks. In the proposed pilot study, the investigators hypothesize that cognitive functioning of AD patients will improve significantly and independently from affective symptoms, when initial and final examinations are compared. The affirmation of the hypothesis would provide not only further insight into the mechanism of action of ECT but also a very important reference point for the development of new treatment options for a so-far incurable disease.

Research on schizophrenia spectrum disorders (SSD) patients with social impairment is essential for improving treatment, enhancing the lives of affected individuals, reducing stigma, and advancing our understanding of this complex psychiatric disorder. A clinical trial focusing on the improvement of social skills in SSD has the potential to transform clinical practice and support systems to better meet the needs of those living with SSD. Because of the role of oxytocin in regulating social behaviors and emotions, the investigator hypothesizes that it is beneficial in addressing the social cognition deficits observed in SSD when combined with psychosocial interventions.

The goal of this subproject is to examine the hypothesized improvement of treatment with chess-based training and sleep enhancement, both together and on their own, in smokers. Participants will undergo fMRI measurements, sleep monitoring. They will then be assigned to one of the four experimental groups, including high-intensity interval training with or without chess-based training.

In this research project, the aim is to discover the role specific brain networks play in the relationship between stress reactions and the desire for alcohol and alcohol consumption. To investigate this question, various brain imaging methods as well as cognitive tasks are combined. Various questionnaires are sampled and brain scans are conducted. Individuals interested in participating in the study have to fulfill certain criteria... * no serious medical or mental health diagnosis * problematic alcohol drinking habits * interested in improving drinking habits ...and undergo various non-invasive procedures * filling out several questionnaires concerning personality and habits * undergoing a mental performance task while being in a brain scanner (MRI) * attempting to regulate their own brain activity while lying in the MRI scanner * filling out an electronic diary for 6 weeks - concerning daily mood, stress, and alcohol habits Participants will be randomly allocated to either one of 2 experimental groups. Both groups undergo the same tasks, receive the same instructions and only differ regarding some aspects of the brain self-regulation task .